Clinical Significance Of CEA/MMP-9 MRNA Expression In Peritoneal Washes From Patients With Gastric Carcinoma

Objective:Peritoneal dissemination is the most common pattern of metastasis in advanced gastric carcinoma.Conventional cytological examination of peritoneal lavage fluid is useful for detecting residual cancer cells in abdominal cavity. However, it lacks sensitivity for the detection. Recent years, molecular diagnosis using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis has been one of the major methods for detecting cancer micro-metastasis. In the present study, we detected CEA and MMP-9 mRNA expression in peritoneal lavage fluid by RT-PCR and tried to find its clinical relevance.Method:The peritoneal lavage fluid of 71 gastric carcinoma patients was collected during the laparotomy. Total cellular RNA was extracted from cell pellets of peritoneal lavage fluid samples and we got the cDNA through the reverse transcriptase experiment. Then, we detected the CEA and MMP-9 mRNA expression quantificationally by RT-PCR method. Besides, we also did conventional cytological examination. We got the positive rate of different examination methods and tried to explore the relationship between the results and clinical characteristics. In addition, we compared the difference of CEA /MMP-9 mRNA expression in peritoneal lavage fluids which were obtained before and after the laparotomy. The follow-up program consisted of 48 patients in our study and lasted for 3-20 months, which may indicate the prognostic significance of CEA/MMP-9 mRNA expression.Results:For 71 patients included in our study,75% patients are male and the average age is 61.86 years. The positive rate of cytological examination is 9.4% and there are 23.9% patients with positive CEA mRNA results. In total,15.4% patients showed positive RT-PCR results both on CEA and MMP-9 and in 55.4% of cases showed positive results either on CEA or MMP-9. For patient of stage I, the positive rate is 12.5%. For patients with invasion depth limited to mucosa, the positive rate is 13.6%. CEA mRNA expression was significantly correlated with depth of cancer invasion, TNM stage, venous invasion, nerve invasion and peritoneal metastasis. MMP-9 mRNA expression was significantly associated with depth of cancer invasion, TNM stage, venous invasion and nerve invasion. Besides, CEA and/or MMP-9 mRNA expression was also significantly associated with depth of cancer invasion, TNM stage, venous invasion and nerve invasion. All of clinical proved peritoneal metastasis cases showed positive CEA mRNA expression, which was higher than the positive rate of cytological examination (100% VS 66.7%)。Three cases with negative expression of CEA mRNA in peritoneal lavage fluid obtained before laparotomy showed positive results in peritoneal lavage fluid obtained after laparotomy. About 77.2% cases showed an increased MMP-9 mRNA level in peritoneal lavage fluid obtained after laparotomy as compared to those obtained before laparotomy. The prognosis of patients with positive CEA mRNA expression was poor than negative cases. The prognosis about MMP-9 mRNA expression showed the same tendency like CEA mRNA results, although had no statistical significance. What’s more, the patients with the positive results both for CEA and MMP-9 mRNAs had the worst prognosis as compared to other patients.Conclusion:Detecting of CEA/MMP-9 mRNA expression by RT-PCR is more sensitive than cytological examination. Combining the results of CEA and MMP-9 mRNA expression may be more accurate for patient prognosis. More cases and long-term follow-up will be useful for confirm the prognosis significance of the method.